ArticleScientific reports2020
Estradiol-dependent axogenesis and Ngn3 expression are determined by XY sex chromosome complement in hypothalamic neurons.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 52 citations in OpenAlex.
- Estradiol modulates neuronal network hyperexcitability in select NDD risk genes.bioRxiv : the preprint server for biology · 2026Article
- Strategies for studying sex differences in brain aging.Trends in genetics : TIG · 2025Review
- Article
- Control of tuberal hypothalamic development and its implications in metabolic disorders.Nature reviews. Endocrinology · 2025Review
- Using Organoids to Model Sex Differences in the Human Brain.Biological psychiatry global open science · 2024Review
- Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain.International journal of molecular sciences · 2022Review
- Epigenetic modifier Kdm6a/Utx controls the specification of hypothalamic neuronal subtypes in a sex-dependent manner.Frontiers in cell and developmental biology · 2022Article
- Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke.International journal of molecular sciences · 2021Review
- X-linked histone H3K27 demethylase Kdm6a regulates sexually dimorphic differentiation of hypothalamic neurons.Cellular and molecular life sciences : CMLS · 2021Article
- On the role of sex steroids in biological functions by classical and non-classical pathways. An update.Frontiers in neuroendocrinology · 2021Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
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Abstract
Hypothalamic neurons show sex differences in neuritogenesis, female neurons have longer axons and higher levels of the neuritogenic factor neurogenin 3 (Ngn3) than male neurons in vitro. Moreover, the effect of 17-β-estradiol (E2) on axonal growth and Ngn3 expression is only found in male-derived neurons. To investigate whether sex chromosomes regulate these early sex differences in neuritogenesis by regulating the E2 effect on Ngn3, we evaluated the growth and differentiation of hypothalamic neurons derived from the "four core genotypes" mouse model, in which the factors of "gonadal sex" and "sex chromosome complement" are dissociated. We showed that sex differences in neurite outgrowth are determined by sex chromosome complement (XX > XY). Moreover, E2 increased the mRNA expression of Ngn3 and axonal length only in XY neurons. ERα/β expressions are regulated by sex chromosome complement; however, E2-effect on Ngn3 expression in XY neurons was only fully reproduced by PPT, a specific ligand of ERα, and prevented by MPP, a specific antagonist of ERα. Together our data indicate that sex chromosomes regulate early development of hypothalamic neurons by orchestrating not only sex differences in neuritogenesis, but also regulating the effect of E2 on Ngn3 expression through activation of ERα in hypothalamic neurons.
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